The blood brain barrier (BBB) is a formidable hurdle that limits the clinical potential of most peptides and proteins to treat CNS disease. Most peptides are poorly transported across the BBB thereby limiting their therapeutic potential. Several neuropeptides have been shown to be active when injected into the brain but fail to exert pharmacological effects when injected intravenously. Many neurodegenerative diseases, cancers, brain infections, and brain traumas could be treated if peptides could enter the CNS. We propose a molecular biological approach to generate new pharmacokinetic activities for peptides so that they can cross into the BBB. If successful, we will create an entirely new, broad class of therapeutics for treatment of CNS diseases. [unreadable] [unreadable] [unreadable]